This program investigates the role that various sensory receptors (mechanical and chemical) play in the control of breathing. State-of-the art neurophysiological, neuropharmacological, mathematical, immunohistochemical and neuroanatomical techniques will be employed to define selective inputs to the respiratory control system with respect to their characteristics and overall influence in shaping the respiratory motor drive and to some extent lung mechanics. The experiments proposed represent natural progression of four of the original projects. Project 1 will isolate and classify individual respiratory sensory receptors, determine if they are activated during normal and/or manipulated (mechanically, chemically) breaths. Project 2 will examine the role that time varying non-linear pulmonary feedback plays in the considerable breath to breath variability in the respiratory pattern. In project 3, a guinea pig model will be utilized to investigate the responses of bronchopulmonary C-fibers to chemical and mechanical stimulation. The brainstem site)s) where reflex effects are mediated will be investigated in Project 4 by conducting systematic microlesion and microinjection experiments in selected nuclei. The four projects will be supported by a Central Core that will provide administrative and technical assistance. With this multi-facet approach the activity of peripheral receptors in response to perturbations can be characterized and traced into the central nervous system. The central connections and interactions can be described and finally, the effect on the respiratory motor output can be determined.